Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells.
Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells.
复制标题
DOI：
10.1007/s12195-012-0253-8
复制
发表时间：
2012-12
影响因子：
2.8
通讯作者：
Vazquez, Maribel
中科院分区：
文献类型：
--
作者：
Dudu, Veronica;Able, Richard A., Jr.;Rotari, Veronica;Kong, Qingjun;Vazquez, Maribel
髓母细胞瘤（MB）是儿童中最常见的脑癌。调节MB入侵的细胞通路对环境的提示仍然不完全清楚。在此，我们研究了迁移反应的人MB衍生的Daoy细胞不同浓度的表皮生长因子（EGF）使用微流控系统。我们的研究结果提供了第一个定量的证据表明，EGF浓度梯度调节MB衍生细胞的趋化性，通过EGF受体（EGF-R）的剂量依赖性的方式。数据表明，较高的浓度梯度导致迁移的细胞数量增加。此外，我们的研究结果表明，EGF诱导的受体磷酸化触发磷酸肌醇-3激酶（PI 3 K）/Akt通路的下游激活，而其下游激活被特罗凯（EGF-R抑制剂）和渥曼青霉素（PI 3 K抑制剂）抑制。用抑制剂处理也严重减少了向增加EGF浓度梯度迁移的MB衍生细胞的数量。我们的研究结果提供了证据，以支持抗迁移疗法的发展，作为可行的策略，以阻止EGF刺激的MB分散。
Medulloblastoma (MB) is the most common brain cancer diagnosed among children. The cellular pathways that regulate MB invasion in response to environmental cues remain incompletely understood. Herein, we examine the migratory response of human MB-derived Daoy cells to different concentration profiles of Epidermal Growth Factor (EGF) using a microfluidic system. Our findings provide the first quantitative evidence that EGF concentration gradients modulate the chemotaxis of MB-derived cells in a dose-dependent manner via the EGF receptor (EGF-R). Data illustrates that higher concentration gradients caused increased number of cells to migrate. In addition, our results show that EGF-induced receptor phosphorylation triggered the downstream activation of phosphoinositide-3 kinase (PI3K)/Akt pathway, while its downstream activation was inhibited by Tarceva (an EGF-R inhibitor), and Wortmannin (a PI3K inhibitor). The treatment with inhibitors also severely reduced the number of MB-derived cells that migrated towards increasing EGF concentration gradients. Our results provide evidence to bolster the development of anti-migratory therapies as viable strategies to impede EGF-stimulated MB dispersal.
登录
查看更多内容
影响因子：
3.7
作者：
Kong Q;Majeska RJ;Vazquez M
通讯作者：
Vazquez M
影响因子：
11.5
作者：
Ono, Mayumi;Kuwano, Michihiko
通讯作者：
Kuwano, Michihiko
影响因子：
2.4
作者：
Ekani-Nkodo, A;Fygenson, DK
通讯作者：
Fygenson, DK
影响因子：
2.8
作者：
Able, Richard A., Jr.;Ngnabeuye, Celestin;Beck, Cade;Holland, Eric C.;Vazquez, Maribel
通讯作者：
Vazquez, Maribel
影响因子：
3.8
作者：
Mosadegh, Bobak;Saadi, Wajeeh;Jeon, Noo Li
通讯作者：
Jeon, Noo Li